Contraceção e risco de tromboembolismo venoso: um estudo caso-controlo

Objetivos: Comparar o risco de tromboembolismo venoso (TEV) entre a 4ª geração e as gerações anteriores de contracetivos orais combinados (COC); analisar a correlação existente entre a idade, índice de massa corporal (IMC) e duração da toma do COC e o risco de TEV. Tipo de estudo: Estudo caso-controlo. Local: Centro Hospitalar doAlto-Ave, Hospital de Braga e Unidade Local de Saúde doAlto Minho. População: Foram estudadas no total 257 mulheres, das quais 122 tinham diagnóstico prévio de TEV e 135 não tinham história de TEV. Métodos: Reviram-se os registos clínicos de mulheres em seguimento por TEV, ocorrido entre 2010 e 2013. As mulheres a tomar COC aquando do evento tromboembólico eram os casos.Os controlosforam as mulheresseguidas em consulta de planeamento familiar,a tomar COC e sem antecedentes de TEV. Resultados: Os COC de 4ª geração não aumentam o risco de TEV comparativamente com as gerações anteriores (OR = 1,77; IC95 0,93-3,38; p = 0,083). Não se observou correlação entre o IMC e o risco de TEV (OR = 1,53; IC95 0,76-3,06; p = 0,234). Por outro lado, a idade (OR = 1,5; IC95 1,02-1,09; p = 0,001) e a duração da toma do COC (OR = 2,41; IC95 1,19-4,87; p = 0,014) estiveram associados a risco de TEV. Conclusões: O risco de TEV depende da idade e duração do uso do COC.Tendo em consideração as limitações do estudo, a interpretação dos resultados deve ser cautelosa, quanto à segurança dos COC de 4ª geraçã

Effect of Weight Loss after Bariatric Surgery on Thyroid-Stimulating Hormone Levels in Patients with Morbid Obesity and Normal Thyroid Function

Background: Several studies have reported that morbid obesity is associated with increased thyroid-stimulating hormone (TSH) levels. However, it is not clear what is the impact of bariatric surgery on postoperative thyroid function. The aim of this study was to evaluate the effect of weight loss after bariatric surgery on TSH levels in euthyroid patients with morbid obesity. Methods: We performed a retrospective observational study of 949 euthyroid patients (86.1% female; age 42.0 ± 10.3 years, BMI 44.3 ± 5.7 kg/m2) with morbid obesity submitted to bariatric surgery (laparoscopic adjustable gastric band, Roux-en-Y gastric bypass, or sleeve gastrectomy). Patients were subdivided in two groups: normal TSH group (TSH <2.5 mU/L) and high-normal TSH group (TSH ≥2.5 mU/L). The impact of anthropometric parameters, comorbidities, TSH, free thyroxine (FT4), free triiodothyronine (FT3), type of surgery, and excessive body weight loss (EBWL) on TSH variation 12 months after surgery was evaluated. Results: The high-normal TSH group (24.3% of patients) included more women, presented a higher BMI, higher systolic blood pressure, and higher FT3 levels. There was a significant decrease of TSH 12 months after surgery that was more marked in the high-normal TSH group (normal TSH group: 1.57 ± 0.49 to 1.53 ± 0.69 mIU/L, p = 0.063; high-normal TSH group: 3.23 ± 0.59 to 2.38 ± 0.86 mIU/L, p < 0.001). In a multivariate analysis, after adjusting for relevant covariates, EBWL, baseline BMI, and baseline FT3 were significantly associated with TSH decrease 12 months after bariatric surgery. Conclusion: Bariatric surgery promotes a decrease of TSH that is significantly greater in patients with high-normal TSH and is independently associated with EBWL after surgery

Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease

Disease progression in IGHV-M CLL with 'good-risk' cytogenetics is frequently associated with co-evolution of 'poor risk' driver mutations and DNA methylation changes.Drug resistance in IGHV-M CLL may be consequent upon the emergence of an IGHV-U cloneThe biological features of IGHV-M CLL responsible for disease progression are still poorly understood. We undertook a longitudinal study close to diagnosis, pre-treatment and post relapse in thirteen patients presenting with cMBL or Stage A disease and good risk biomarkers (IGHV-M genes, no del(17p) or del(11q) and low CD38 expression) who nevertheless developed progressive disease, of whom ten have required therapy. Using cytogenetics, FISH, genome-wide DNA methylation and copy number analysis together with whole exome, targeted deep- and Sanger sequencing, at diagnosis we identified mutations in established CLL driver genes in nine (69%), non-coding mutations (PAX5 enhancer region) in three, and genomic complexity in two patients. Branching evolutionary trajectories predominated (n=9/13), revealing intra-tumoural epi- and genetic heterogeneity and sub-clonal competition prior to therapy. Of the patients subsequently requiring treatment, two had sub-clonal TP53 mutations that would not be detected by standard methodologies, three qualified for the very-low risk category defined by integrated mutational and cytogenetic analysis and yet had established or putative driver mutations and one patient developed progressive, therapy-refractory disease associated with the emergence of an IGHV-U clone. These data suggest that extended genomic and immunogenetic screening may have clinical utility in patients with apparent good risk disease.Leukemia accepted article preview online, 05 February 2016. doi:10.1038/leu.2016.10

Experimental assessment of hybrid mould performance

Hybrid moulds are a novel approach for rapid tooling of injection moulds that combines conventional machining for the mould structure and rapid prototyping techniques for the moulding blocks (core and cavity). In this study, two routes were used for producing the moulding blocks: selective laser sintering of stainless steel-based powder (hard tool) and epoxy resin vacuum casting (soft tool). The experimental work was based on a complex tridimensional commercial part. Themouldings were made in polypropylene, and the processing performance was monitored online in terms of pressure and temperature at the impression. The performance of the moulding blocks was analysed in terms of thermal and cycle performance and structural integrity. The epoxy tooling route is more adequate for fine detailing than selective laser sintering but is not adequate for parts with extensive ribs or deep bosses. The structural integrity of the less costly epoxy composite can be compromised during ejection, this suggesting the need to evaluate the stress field by simulation at the design stage of the mould.Fundação para a Ciência e Tecnologia (FCT) - POCT

Influence of anatomic reference on the buccal contour of prosthetic crowns

During clinical practice, when performing prosthetic rehabilitation with single crowns, improper reproduction of the dental contour by the dental laboratory is a common occurrence. Therefore, the present study evaluated the fidelity of the reproduction of the buccal contour in an upper left canine performed by three Dental Prosthesis Technicians (DPT) using the indirect laminate veneer technique. First, the DPTs confected the veneers based on a model obtained from the upper arch of a dental dummy, containing a replica of an upper left canine with a prosthetic preparation for a laminate veneer. Then, the same DPTs received other identical models, now with the replica of the upper left canine with no preparation, to be used as an anatomical reference for confecting the laminate veneers. The laminate veneers were then bonded to the plaster models and had their buccal contour individually measured. Measurements were also made of the buccal contour of the reference canine. The data were analyzed by ANOVA and the t-test (p = 0.05). Results showed 100% of buccal overcontour when the laminate veneers were compared to the reference canine, regardless of which DPT confected the veneer and regardless of using or not the anatomical reference. The DPTs who participated in the present study were unable to acomplish a faithful anatomical reproduction of the buccal contour, creating an overcontour in all samples. This situation may be responsible for increasing the probability of periodontal and esthetic harm in clinical practice